Benzene ring-containing glucose derivative and application thereof

A technology of glucose derivatives and benzene rings, applied in the fields of radiopharmaceutical chemistry and clinical nuclear medicine, can solve the problems of slow clearance, tumor uptake and target/non-target ratio to be further improved, and achieve high uptake, tumor/non-target ratio Good results

Active Publication Date: 2021-01-05
BEIJING NORMAL UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0005] The application number is 202010032704.2, and the invention patent application with the publication number CN111138504A discloses a 99m Tc-CNPEDG complex and its preparation method and application, which introduced a benzene ring between the chelating group (isocyano group) and the targeting group (D-glucosamine), successfully prepared 99m Tc-CNPEDG complex, the preparation method is simple, 99m Tc-CNPEDG has high uptake and good retention in tumors, but its clearance in blood is slow, while tumor uptake and target / non-target ratio still need to be further improved

Method used

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  • Benzene ring-containing glucose derivative and application thereof
  • Benzene ring-containing glucose derivative and application thereof
  • Benzene ring-containing glucose derivative and application thereof

Examples

Experimental program
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preparation example Construction

[0045] (2) 99m Preparation of Tc-CNBDG

[0046]Dissolve 1mg of sodium citrate and 1mg of L-cysteine ​​in an appropriate amount of normal saline, and add 0.06mg of SnCl to it 2 2H 2 O, adjust the pH of the solution to 6.0, and then sequentially add 0.5 mg of the ligand CNBDG and 1-2 mL of freshly rinsed Na 99m TCO 4 , react at 100°C for 20 minutes to get 99m Tc-CNBDG complex.

[0047] prepared by the above method 99m The radiochemical purity of the Tc-CNBDG complex is greater than 90%, and the stability in vivo and in vitro is good. It has high uptake and good retention in the tumor site of tumor-bearing mice, and the target / non-target ratio is good. publicly available with the prior art 99m Tc-CNPEDG and 99m Tc-(CN5DG) 6 + compared to, 99m The tumor / muscle and tumor / blood ratios of Tc-CNBDG are higher, which achieves the invention purpose of increasing the target / non-target ratio of this type of imaging agent, and is conducive to popularization and application as a ...

Embodiment 1

[0051] This embodiment provides a 99m Tc-labeled phenyl ring-containing glucose derivatives, referred to as 99m Tc-4-CNPeDG, the structural formula is as follows:

[0052]

[0053] Its preparation steps are as follows:

[0054] 1. Synthesis of 4-CNPeDG:

[0055]

[0056] Weigh 0.269g D-glucosamine hydrochloride and 0.055g sodium hydroxide in a 25mL round bottom flask, add 20mL of anhydrous methanol, stir at room temperature until the solid is completely dissolved, then add 10mL containing 0.337g 4-( 2-isocyanoethyl) benzoic acid-2,3,5,6-tetrafluorophenyl ester in methanol, and then continue to react at room temperature for 24h. After the reaction, the solvent was distilled off under reduced pressure, and the residual solid was separated and purified by silica gel column chromatography (dichloromethane:methanol=5:1). After drying, 0.13 g of a light yellow solid was obtained, with a yield of 37%.

[0057] 1 H NMR (400MHz, methanol-d4): δ7.83 (dd, J = 15.8, 8.5Hz, 2H),...

Embodiment 2

[0063] This embodiment provides a 99m Tc-labeled phenyl ring-containing glucose derivatives, referred to as 99m Tc-4-CNMBDG, the structural formula is as follows:

[0064]

[0065] Its preparation steps are as follows:

[0066] 1. Synthesis of 4-CNMBDG:

[0067]

[0068] Weigh 0.220g of D-glucosamine hydrochloride and 0.045g of sodium hydroxide in a 25mL round bottom flask, add 10mL of anhydrous methanol, stir at room temperature until the solid is completely dissolved, then add 10mL of 0.290g of 4-iso Methanol solution of cyanomethylphenylacetic acid-2,3,5,6-tetrafluorophenyl, and then continue to react at room temperature for 24h. After the reaction, the solvent was distilled off under reduced pressure, and the residual solid was separated and purified by silica gel column chromatography (dichloromethane:methanol=5:1). After drying, 0.150 g of a light yellow solid was obtained, with a yield of 50%.

[0069] 1 H-NMR (400MHz,D 2 O): δ7.42(d, J=8.2Hz, 2H), 7.37(d, J...

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Abstract

The invention relates to the technical field of radiopharmaceutical chemistry and clinical nuclear medicine, in particular to a benzene ring-containing glucose derivative and an application thereof. The benzene ring-containing glucose derivative has a structure as shown in a general formula (I), and a radioactive preparation obtained by labeling the benzene ring-containing glucose derivative withradionuclide has high uptake in tumors and good tumor/non-target ratio, and is a novel tumor radiopharmaceutical with popularization and application values.

Description

technical field [0001] The invention relates to the technical fields of radiopharmaceutical chemistry and clinical nuclear medicine, in particular to a glucose derivative containing a benzene ring and an application thereof. Background technique [0002] Cancer is a serious threat to human health. Early detection and treatment of cancer is of great significance for improving survival rate, reducing mortality, reducing patient pain, and saving treatment costs. Nuclear medicine imaging technology can diagnose tumors at the molecular level, and has the advantages of high sensitivity, good specificity, and non-invasiveness. Combined use of PET) and single photon emission tomography (SPECT) with CT, etc., radionuclide tumor imaging has become one of the advantages of nuclear medicine diagnosis. [0003] Glucose is the main energy substance for cell metabolism, while malignant tumor cells proliferate rapidly and have active metabolism, and their demand for glucose is much higher ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H13/08C07H5/06C07H1/00C07F13/00C07B59/00A61K31/7135A61K51/04A61P35/00A61K103/10
CPCC07H13/08C07H5/06C07H1/00C07F13/00C07B59/005A61K51/0491A61P35/00C07B2200/05A61K51/0497A61K51/0476A61K51/025
Inventor 张俊波甘倩倩王倩娜张旭冉阮晴江雨豪王学斌唐志刚陆洁张站斌
Owner BEIJING NORMAL UNIVERSITY
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